Asthma and other respiratory diseases have long been treated by the inhalation of appropriate medicaments. For many years the two most widely used and convenient choices of treatment have been the inhalation of medicament from a drug solution or suspension in a pressurised metered dose inhaler (pMDI), or inhalation of powdered drug, generally admixed with an excipient, from a dry powder inhaler (DPI). Following strong concern about the link between depletion of the earth's ozone layer and chlorofluorocarbon (CFC) emissions, the use of these materials in pressurised inhalers is being phased out and interest in DPI systems has been stimulated.
Quite a number of DPI systems or components for DPI systems have been described including those described in, for example, GB 2242134 (Davies et al.), U.S. Pat. No. 5,192,548 (Velasquez et al.), U.S. Pat. No. 5,619,984 (Hodson et al.), U.S. Pat. No. 5,657,748 (Braithwaite), WO 98/41255 (Jennings et al.), WO 01/21238 (Seppala), and US 2006/0081246 (Goede et al.). In practice most DPIs use either bulk powder reservoirs or individual pre-measured doses sealed within individual containers in the form of capsules or blisters, such as blister packs and blister strips.
There are, however, problems associated with accurately metering a measured small quantity (e.g., 500 micrograms or less) of powder from a bulk reservoir within an inhaler. With many drugs, e.g., potent drugs, this introduces the necessity to add excipients, such as lactose powder, to significantly increase the quantity of powder to be metered. Such excipients are however generally undesirable as they can pose subsequent powder deagglomeration problems and can cause dryness and other unwanted effects in the patient's mouth.
Furthermore, ingress of moisture (ambient moisture and/or moisture from a patient's breath e.g., inadvertently exhaled into the inhaler) into e.g., the bulk powder reservoir can pose a serious problem. Many biologically active substances, such as medicaments, delivered by inhalation are susceptible to physical or chemical change and/or degradation in the presence of moisture vapor. For example, the powdered particles may re-crystallize in the presence of adsorbed moisture vapor, which may lead to an effective increase in the median particle size of the powdered material, which in turn may lead to reduced penetration of the particles into relevant delivery sites in the lung, e.g., the lower airway passages in the lung.
DPIs where the powder supply, e.g., powdered medicament, is provided in the form of capsules or blisters generally have somewhat better moisture protection, due to the fact that each individual dose is sealed off, where typically a dose on a carrier component is covered and sealed with a lid component. The manufacturing of such capsules, blister packs or blister strips, including accurately metered, small quantities of powder per capsule/blister for use in a DPI, can be difficult and/or quite expensive. Furthermore, DPIs using such a powder supply normally require complex mechanisms for opening the individually sealed capsules or blisters (e.g., mechanisms for peeling the lid off, puncturing the capsule/blister, etc.).